I think we should be live now. Good morning, everyone. Welcome to Guggenheim 3rd Annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the senior biotech analysts here at the firm. It is my pleasure to welcome our next presenting company, Abivax. From the company, we have two executives here with me right now. We have Chris Rabbat, the Chief Medical Officer, and then we also have Michael Nesrallah, who is the Chief Commercialization Officer. Gentlemen, thank you so much for your time. We always appreciate it. Chris, why don't you make some opening comments? You were at UEG. I was there as well. Some new data got presented. Love to hear some of the key updates and the highlights from the meeting.
Yeah. So, yeah, thanks for the time. UEG was a great meeting for us. We presented our maintenance data for the first time to the gastroenterology community. We presented it as a whole, and then also the patients that were AT-naïve and the patients that are experienced. And what you will notice in our data is that one of our endpoints, endoscopic remission, is basically 50% of our patients are in endoscopic remission at the end of maintenance, which is cross-trial, head and shoulders above anything that has ever been seen. And it was like a perfect storm. At UEG, the VERDICT trial read out, which is a treat-to-target trial. It has been going on for some time, and basically determined that the best outcome measure to predict long-term outcomes, meaning reducing surgery, reducing hospitalization, is endoscopic remission.
The STRIDE-III guidelines were also updated at the same meeting to make endoscopic remission the long-term treatment target that should guide therapy in ulcerative colitis and Crohn's disease. So, us presenting our maintenance data at that same meeting, highlighting endoscopic remission, was really just a stroke of, I think, fortune for us.
Got it. Can you talk a little bit about these guidelines? Because I think they have evolved over time. It used to be focused on clinical remission. I mean, it was symptom remission, and now ES. What does actually that mean? And obviously, your data on the endoscopic remission is very good. How does it, all of this is going to evolve over the next, let us say, four or five years as these guidelines get sort of adopted?
Yeah. The STRIDE guidelines, this is the third version, and they're meant to guide clinicians on how to evaluate whether or not the patient needs more therapy or a different therapy, and when, right? Because that's really been the problem for some time, is that getting started on advanced treatment is hard enough, but then when they stop responding, when do I decide that this is not working for them? That was always kind of subjective. They're trying to make it more objective, and that was the purpose from the beginning. Now, it makes it very clear that symptomatic improvement is the important short-term target. They also have adjunctive targets like bowel urgency, fatigue, things like that. Again, the long-term target that should guide treatment choice and change, right, is endoscopic remission.
So that means that if I have a patient that's doing well, but their endoscopy is not quite where I need it to be, I may need to switch their therapy to get them there, because that ES0 matters for that patient in the long term.
Okay. Then with regard to a key presentation that you did where you announced the subgroup data for AT-naïve, AT-experienced, and across different settings, right? Can you just maybe put that in perspective? Number one, the severity of the patients. Number two, what you saw. Then talk about, because now you have an opportunity to engage with many KOLs, right? What is their perception of the profile of the product?
Yeah. We analyzed our data a priori, so part of the SAP, looking at patients that had never failed an advanced therapy, and our data there is exceptional, right? The efficacy is second to none across all the endpoints, including endoscopic remission. The data in the advanced treatment failure patients is the same. It's exceptional. It's as good or better than anything that's ever been seen. We also analyzed it by number of failures, one failure, two failure, three failure, four plus failures, and then we broke it down to JAK failures, just like we did in induction, and no other company has broken out their data that way. I think we can all suspect why, is that once you get past two failures, things don't look so good. For ours, the efficacy was maintained, right? So all the way out to four plus failures.
Now, the Ns do get small when you get out there, but those patients are getting to remission in about a third of the patients, which is unheard of in our disease state.
And maybe just to add on, when you talk about clinicians' perspectives on our value proposition, as the commercial guy, I will tell you, it is a privilege to be able to work on obe. From the exceptional efficacy data, the safety profile, when you think about we do not currently anticipate any testing or monitoring, it is oral, quick onset of action. This drug has all of the attributes physicians are looking for, and they respond in kind. When they see symptomatic response separating at week one, when they understand that we are not currently anticipating testing or monitoring, that connotes not only safety, but simplicity, which is highly valued, especially in the community. The value proposition resonates across the board, but it definitely starts with the efficacy.
Yeah
And the endoscopic remission.
Michael, maybe just picking on that. What is the perception in terms of which line of treatment this drug is going to be adopted by this physician? What do you hear?
That's a great question, and it's one that I've spent a lot of time thinking about, and we actually hear from the podium KOLs pontificating on this. In marketing, typically you look at a drug and you say, "Where does it have a unique value proposition?" The reality is, we work exceptionally well in the AT-naïve population. As Chris Rabbat was just saying, we also work exceptionally well in the refractory population. What you heard one of the KOLs say from stage at UEG was, "Look, there's a significant reason to be using this in later lines, but it would be a mistake to only use it there, because there is such an unmet need in the first line as well." You want to start strong, and you want to stay strong.
With obefazimod, they have the opportunity to use this across lines of therapy, and I genuinely believe that's the makings of becoming a standard of care in the space.
Got it. I would have to assume that as these guidelines get adopted, more push toward ES equals to zero, you want to treat early with the best available options.
Sure. Absolutely.
that you have, right?
For sure. Absolutely. Getting to ES0 early, actually, there's data showing that that's even better than ES0 late, right? You want to get them to ES0 as soon as possible. That's going to give them the best outcome. If you wait till they fail two or three other therapies, first of all, you're going to have a lower percentage get there.
Yeah.
Even then, there's a lot of damage that's been done already by then.
Yeah.
It's also important to note, there's a lot of patients out there that are moderate to severe and not currently on an advanced therapy. When you look at the profile of obe, the fact that we're safe and effective and a pill, no anticipated testing or monitoring, that's a much lower bar to start an advanced therapy than the conventional therapies they're on today. I think it will be a very helpful option for physicians who are trying to get patients who need an advanced therapy on one.
Got it. You touched on safety a couple times. What is the perception? Any chatter still around these NMSCs and non-NMSCs that came out?
Yeah, there really isn't. It never comes up. We talk to KOLs every day. We've talked to over 200 of them together on different advisory boards and different forums, and they don't even blink at it. These are numbers that they're used to seeing. The malignancy rates are consistent with the background in the UC population. We showed that very clearly, and we don't think there's any lingering questions about that.
Got it.
I think it was helpful for the investor community when we were able to characterize the fact that these events are consistent with the background UC population. But the clinicians, they don't even bat an eyelash when they see the safety profile. It's unremarkable to them. Those things don't stand out as anything of concern.
Yeah. What stands out is they're not seeing the adverse events that they're used to seeing with some of the other treatments, like herpes zoster and opportunistic infections and things like that, where we don't see any of that in our dataset because the MOA is not immunosuppressive, right? It balances the immune system as opposed to suppressing it.
Got it. What is the guidance for the NDA submission? I think you've said by the end of this year. Are you tracking for that? I think you have made some comment about supplemental package. Just tell us what that package would entail and when that will be submitted.
Yeah. We're going to be submitting by the end of the year. We've got a team of people working on that. We're working very closely with former FDA officials that were very senior at the gastro division. It's reviewing every section with our team and adopting their changes. We're confident that not just the timing, the content is going to be tip-top shape. We're filing by the end of the year, and what we agreed with FDA at the pre-NDA meeting was that one of our batches needed another month of stability data. They agreed to allow us to submit that 30 days later after the NDA submission and have no change in the clock for the PDUFA date. That was the sort of the thing that we had explained before.
Okay. Very good. Michael, maybe a couple questions for you. Just help me understand the UC market dynamics, how you think this market is going to evolve, because there is talk about combination, whether it's the biologic combination or the oral combination coming in. Obviously, your products look as good as a combo. Talk about that, some of the payer work, obviously the effort that you are putting in in building the infrastructure to launch.
Sure. I will start with your last one first in terms of building infrastructure. Really exciting. I have had my leadership team in place now for about three, four months in total, and they have already started to build out their leadership team. We have actually scaled the commercial team at a rather impressive clip, and the important thing is we are bringing in the best-in-class talent from across the industry, all with experience in IBD, which will pay dividends for us. Our Head of Pricing and Access, our Head of Patient Services, both coming from AbbVie, our Head of Marketing, our Head of Commercial Operations, Sales, and Accounts coming from Takeda, all with a wealth of experience in IBD and scaling. The team knows what they are doing, and we are getting ready for a best-in-class launch.
When we think about what we are learning in our early days and how we are thinking about our value proposition, it really comes back to a lot of the discussion we have already had around our efficacy profile, so the endoscopic remission with half of our patients in endoscopic remission in their high-dose arm, that is the new bar for any emerging therapy, combo or mono, that they have to reach that with a safety profile that is as compelling as ours. That is the standard that we are setting with this product. I think not only for physicians, but as you asked about payers, I think as physicians start to learn more about our clinical data and then ultimately get clinical experience, there is going to be a willingness to create access.
I think at launch, it is reasonable to expect that we will come in and see a lot of our utilization in second line plus, but I think more and more early after launch, you are going to see our access growing in first line as well as the clinical experience, and that is why our patient services programs will be so critical.
How big will be your team, the sales force that would be needed, and how many GIs you are going to be targeting?
Yeah. If you think about the field teams in this space, you roughly see anywhere between 120- 150 reps in total. That's sort of a range, and we're going to operate within that space. In terms of a gastroenterologist, so there's 18,000 board-certified GIs in the U.S. Of that, you're probably looking at around 12,000 that are treating IBD in any capacity, maybe 8,000 in total that are meaningfully treating IBD patients. We'll stratify those, and we should be able to reach that broader audience, not only with our live promotion and face-to-face with our field teams, but also with a multi-channel approach. That'll be engaging.
Okay. Got it. Very helpful. Then maybe I wanted to touch a little bit on the Crohn's side first, then I'll come back to more questions on the commercial. With regard to the Crohn's disease, how is the enrollment? I think there is some change in terms of how you are enrolling. Just talk about that. I think you have looked at the data on a blinded basis. Give a little bit flavor there, what exactly you have looked and what do you see?
Yeah. The enrollment has definitely picked up. We're seeing some great uptake in the new countries that we opened. All the sites that we're using have all had experience with obefazimod during the ABTECT phase III program in UC, where we believe they performed well, so we trust them. We know they know how to run clinical trials, they know how to deal with patients. So we have a lot of confidence there. We are going to be reading out the data mid-next year, and what was the last thing you said?
The blinded data.
Yeah, the blinded data. We don't necessarily want to talk too much about the blinded data, but what we have said is that we don't see any sort of red flags or any reason to stop. Everything is pointing in the right direction.
Got it. When you I mean, you don't have to answer, but I still ask. When you look at the blinded data, you look at some of these primary endpoint like CDAI, or you focused on more histology?
Yeah. It's a good question, and I can answer that by also thinking about, well, what are we going to look at when the trial's finished, right? And the important part is that we consider the totality of the data, not any one endpoint. So yes, we'll have change in CDAI. We'll also have endoscopic response. We'll have endoscopic remission. We'll have clinical remission. We'll have PRO2, the symptom output that the EMA uses. And we'll look at all of that to try to understand the competitiveness of the profile and the likelihood of success in phase III, and we'll make a decision based on that.
I see. Very helpful. What is the endpoint for Crohn's disease? Because I think I saw a combination data that was presented by AbbVie where they didn't report CDAI, so I'm just curious, what is the endpoint in Crohn's?
Yeah. The preferred endpoint from the regulators is, from FDA, is CDAI remission, so Crohn's Disease Activity Index remission, which is a score of less than 150, and endoscopic response, which is a SES-CD improvement of 50% on the score. That is usually a co-primary endpoint for both induction and maintenance, meaning that you test them individually, not in the same patient, right? They are co-primaries. It is different than UC, where there is a composite endpoint where you take the symptoms and the endoscopy and you put it together in clinical remission. In Crohn's, for whatever reason, there is some history and a story behind this, but we ended up with two separate co-primary endpoints that they are asking for.
Okay. With regard to the dose, I think there are many drugs that are approved that need a higher dose in Crohn's disease. What is that dynamic for obe? I know you are testing a lower dose of 12.5, but are you going higher on the dose?
Yeah. We are testing three doses versus placebo, and as is typical at a phase IIb dose-finding study, we included the high dose from UC, which is 50 mg, the 25 mg dose, and the agencies asked us to include a third dose, and we wanted to show the minimum effective dose. When we made that decision at the time, we did not have phase III UC data. We only had phase II UC data. If you remember, thinking back there, it was not really clear whether 25 mg or 50 mg was better, right? We decided to include 12 and a half at that time. We do not expect to see much efficacy on 12 and a half now having the UC data in hand. But yeah, still we will have the three doses versus placebo.
What is the path forward in Crohn's? You need one study, two study after this, and when those studies could start?
Yeah. That's a very good question, and it's going to come down to a regulatory discussion. But ideally, we would take one dose in one phase III trial, a placebo-controlled induction trial feeding into a responder maintenance trial, and we'll hopefully have an open-label induction arm feeding that as well. We're really looking for, yes, a comprehensive high success rate Crohn's program, but we do want to go fast. We are thinking about the LOE, and we want to get to market with a drug that we think can help a lot of patients.
Got it. Then moving on to the combination strategy. Again, like I mentioned, there is a lot of talk about the combination, whether it's the biologic or the oral. You guys are running a combination program in preclinical setting. So talk about, number one, when you will present the data, what we will learn from those data, what are the mechanism that you are evaluating with obe?
Yeah. Yes, we're running a number of preclinical studies to try to understand the additive and potentially synergistic effects between obefazimod and other mechanisms of action so that we can help inform our decision on choosing one MOA and moving forward with that into a UC and CD program. We are going to make a decision by the end of this year, and then in early January, before JPM, we'll be putting out a press release that's going to lay out our strategy over the next year, which will include information on the combination that we will be pursuing.
We want to make a decision, get access to a molecule in some way, whether it's a partnership, whether it's a license, whether it's an acquisition, one of those things, so that we can start the preclinical combination tox study in animals, which is kind of the rate-limiting step to get into a proof of concept in UC patients, which we want to get to as soon as possible. We think we have a chance to be the first company with an all-oral combination in a UC patient. So that's our goal.
With obe as a backbone.
That is right.
Got it. You actually have tested preclinically S1P, right?
Yes.
With obe. What were the findings there?
Yeah.
What additional information we learn from, let's say, these other four mechanisms that you are evaluating?
Yes. In terms of the mechanisms, we did S1P early on, and now our strategy has really sharpened. Yes, we want it to be oral. We want it to have synergistic efficacy, and that is what we saw with the S1P. However, the third thing is we want the safety profile and the labeling of the combination partner to be similar to obefazimod.
Yeah.
We have no testing, no monitoring. We do not expect any kind of boxed warning or anything like that. S1Ps come with those pre-initiation requirements that we do not want to inherit. That gives you an idea. S1Ps, the MOA is not the same, but it is similar to alpha-4 beta-7, right, where it is a lymphocyte trafficking. Alpha-4 beta-7, I think, is the leading candidate. There is also the oral IL-23 receptor antagonists that we are looking at. We think there is some overlap in the MOAs there. Also, there are only peptides available there. There might be some formulation challenges. These are not showstoppers. We want to choose what we think is going to be the best combination based on all the factors that I mentioned.
Got it. Could you review the oral competitive landscape for us? We saw data from Gilead oral alpha-4 beta-7. They actually went out and acquired an IL-23 oral as well. Most likely they are going to combine it.
Yes.
What about the Lilly molecule? There are some other stuff that is out there. How do you see it?
Yeah. There's a number of alpha-4 beta-7s, right? There's the Gilead, who I guess is in the lead now, right? Lilly had run a phase II study, but they didn't hit the endpoint, so they're running another larger one now with their molecule. There's also some preclinical ones that are privately held that don't have human clinical data yet. That's sort of one of the limitations. There's also a number of oral small molecules available in the IL-23 receptor antagonist space. You saw Gilead just pick one up. There are others. There's also PDE4s, which are kind of making a comeback. We saw some good data from mufemilast, which is from a company in China. They have proof of concept in humans. There's a number of other PDE4s. There's also the aryl hydrocarbon receptor modulators.
There's a couple of companies that have those, also privately held. Well, one's privately held. I think the other one's public that we've looked at as well. But again, the further you go back to before human proof of concept, the harder it's going to be for a combination program. Ideally, we would have an MOA that has that already.
Got it. Got it. Well, I think that's all I had for you guys. Well, thank you so much.
Thank you. Thank you. Thanks, everybody. Thanks, everyone.